Pneumonia is the leading infectious cause of hospitalization and death in the United States (US). Streptococcus pneumoniae is the main bacterial cause of pneumonia. The introduction of a seven-valent pneumococcal conjugate vaccine (PCV7) into the US infant vaccination schedule in 2000 led to substantial reductions in the incidence of invasive pneumococcal disease (IPD) and pneumonia in children <2 years. By preventing nasopharyngeal colonization with pneumococcal vaccine serotypes, PCV7 also interfered with the transmission of bacteria from person to person. Concurrent declines in the incidence of pneumococcal diseases among unvaccinated subjects provided strong evidence for indirect protection through reduction of such transmission. Although modest increases in the incidence of pneumococcal diseases caused by non- vaccine serotypes (i.e. replacement) was observed in the general population, a more intense replacement was observed among persons with high-risk conditions for pneumococcal diseases. A 13-valent pneumococcal conjugate vaccine (PCV13) replaced PCV7 in the infant vaccination schedule in 2010. This new vaccine was introduced to prevent a large portion of remaining serious IPD, including replacement disease, much of which is due to the 6 additional serotypes included in PCV13. In December 2011, FDA approved PCV13 for use among adults aged e50 years, based on immunogenicity data only. However, formal national recommendation for its use in adults has been postponed until additional information on the effects of PCV13 on clinical outcomes and the indirect effects of the infant vaccination program in unvaccinated groups become available. Preliminary data from surveillance systems suggest that IPD caused by the 6 additional PCV13 serotypes has started to decline in young children, and similar reductions have been noted among unvaccinated adults. Nevertheless, IPD is rare compared with pneumococcal pneumonia, a major driver of the vaccine cost- effectiveness. Whether routine vaccination of infants with PCV13 has a substantial impact on the incidence of pneumonia in unvaccinated subjects is unknown. If vaccination of infants with PCV13 has already resulted in substantial indirect benefits among unvaccinated adults, then the potential effectiveness of a new adult vaccination program may be substantially limited. Moreover, whether indirect protection has been conferred to adults with high-risk conditions for pneumococcal diseases remains unclear. We propose to conduct a series of studies with the following specific aims: 1) Test the hypothesis that routine vaccination of infants with PCV13 resulted in declines in pneumonia hospitalizations among unvaccinated children and adults; and, 2) Test the hypothesis that routine vaccination of infants with PCV13 reduced pneumonia hospitalizations among unvaccinated adults with high-risk conditions for pneumococcal infections. The evaluation of the indirect effects of the PCV13 infant vaccination program is a critical step for the formulation of pneumococcal vaccination policies.